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Screening methods using sulfamethazine for determining acetylator phenotype
Author(s) -
Souich Patrick,
McLean Allan J.,
Stoeckel Klaus,
Ohlendorf Dieter,
Gibaldi Milo
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1979266757
Subject(s) - urine , chemistry , sulfadimidine , urinary system , chromatography , medicine , biochemistry
Analysis of sulfamethazine (SMZ) kinetics in man has revealed complexities including wide intersubject variability. In our study, an attempt was made to assess the potential influence of changes in nonmetabolic parameters (absorption and urinary elimination rate constants) on the markers of acetylation capacity normally used in clinical screening procedures to determine phenotype. Seven normal subjects were classified as slow (SA) or fast acetylators (FA) according to their metabolic rate constant for SMZ (Km), plasma SMZ half‐life, and percentage of N‐acetyl SMZ in a 6‐hr blood sample (PI 6 ), a 5‐ to 6‐hr urine collection (UI 6 ), or a 6‐hr total urine collection (UI 6 ). Computer simulations were applied to baseline SMZ kinetic data from these subjects, varying nonmetabolic kinetic parameters over experimentally defined ranges singly, or in parallel with 1 or more of the other parameters. The simulations indicate that all the usual phenotyping procedures were sensitive to changes in absorption and urinary elimination rate constants. While these predictions require experimental confirmation, results show that the PI 6 method is least sensitive to such changes, suggesting this method may minimize errors in phenotyping screening.